The vagus nerve is a member of a group of nerves commonly referred to as the cranial nerves. Scientifically, the vagus nerve has been designated as the tenth cranial nerve. There are two of these mixed nerves that act to provide both motor and sensory functions. Each vagus nerve contains both somatic and autonomic branches, however within the body the autonomic function predominates. Vagus nerves are parasympathetic in nature making up 75% of all parasympathetic fibers passing to the thoracic and abdominal regions of the body. As is the case with most nerves, vagus nerves contain both efferent fibers, carrying impulses from its origin in the medulla obligata of the brain to a tissue or visceral organ, as well as afferent fibers, which carry the impulse from the organ back to the brain itself. With vagus nerves, 80% of the fibers are afferent as opposed to efferent. This aids in their active response to the many reflex actions in the body during parasympathetic control. As a whole, the two vagus nerves are very large and work to stimulate a great number of tissues in the body. Vagal stimulation works to innervate the heart, lungs, esophagus, stomach, small intestine, liver, gall bladder, as well as the upper portions of the ureters.
As the vagus nerves become stimulated, the hormone acetylcholine is released at the vagal endings. Therefore, vagus nerves are said to be cholinergic (a term signifying the hormone by which it secretes). This is in contrast with adrenergic systems which cause the release of epinephrine and norepinephrine. It is the release of acetylcholine, rather than the passing of nerve impulses that directly initiates the specific response within the organ.
In the heart, parasympathetic vagus nerves are distributed mainly to the SA node and the AV node. Although stimulation does occur to both atrial and ventricular muscle, the majority of its action occurs in the nodal areas. Release of acetylcholine to these areas results in both a decrease in the rate or rhythm (e.g., the degree of heart rate variability is heavily influenced by vagal stimulation) of the SA node, as well as a decrease in the cardiac impulse transmission into the ventricles. Consequences of these actions include decreases in heart rate, cardiac output, ventricular contraction, arterial blood pressure, as well as overall ventricular pumping.
More specifically, the right vagus innervates the S-A node, the atrial muscle and, to a much lesser degree, the A-V node. The left vagus nerve innervates the S-A node and atrial muscle to a lesser degree than it innervates the A-V node. It is well known to physiologists that stimulation of the right vagus nerve predominately slows the S-A node rate and thereby reduces heart rate. Stimulation of the left vagus nerve produces some slowing of the S-A node, prolongation of A-V conduction and partial or total A-V block.
Regarding left vagal stimulation, U.S. Pat. No. 5,916,239, entitled “Method and apparatus using vagal stimulation for control of ventricular rate during atrial fibrillation”, to Geddes, et al., issued Jun. 29, 1999 ('239 patent), states that “low-frequency left vagal stimulation causes a dramatic shortening of the duration of the atrial monophasic action potential, indicating shortening of the atrial refractory period” and that “[a]lthough the left vagus nerve affects atrial rate to a lesser degree, transmission of excitation across the A-V node is largely regulated by the left vagus nerve” (col. 1, I. 59-61). The '239 patent also discloses that “atrial fibrillation can be allowed to persist and that stimulation of the left vagus nerve, as opposed to the right vagus, is necessary and sufficient to effectively control the ventricular rate during atrial fibrillation” (col. 2, I. 55-58). However, the current theory on atrial fibrillation is NOT to let it persist, since it can cause poor hemodynamics and permanent remodeling of the heart, but instead to terminate it quickly. Thus, the present invention is directed towards controlling the right vagus nerve, particularly those affecting the cardiac branch, so that the Sinus Node, the associated conduction system and perhaps even the length of atrial refractory, can be slowed.
The '239 patent discloses a device having a first pair of electrodes in the right ventricle for providing ventricular pacing and sensing, a second pair of electrodes in the right atrium for atrial pacing and sensing, and a third pair of electrodes “attached or adjacent to the left vagus nerve” (col. 4, I. 54-55) for stimulating left vagus nerve and controlling ventricular rate. The '239 patent discloses “a catheter electrode in the right atrium and ventricle and another electrode on the left vagus nerve” (col. 11, I. 33-35). The '239 patent further states that “the principle can be applied using catheter electrodes” by using “a catheter electrode in the right pulmonary artery to stimulate the left vagus nerve, as described by Cooper et al. (Circ. Res. 1980, 46:48-57)” (col. 11, I. 35-38).
The '239 patent also refers to a paper by Bilgutay et al. (J. Thoracic Cardiovas. Surg. 56(1):71-82, July, 1968) In his experiments, Bilgutay et al. indicated that the right vagus nerve was stimulated [in the neck of dogs using a nerve cuff] because its distribution is known to be mostly to the sinoatrial node area, and further that stimulation of the left vagus nerve (in a dog with complete heart block) slowed the ventricular rate and suggest that this may be effective in nodal tachycardias. Bilgutay defined the optimal heart rate as the slowest heart rate that could be attained by vagal stimulation without causing A-V dissociation or complete heart block. (col. 2, I. 4-30). That is, too much stimulation (e.g., amplitude, pulse width or frequency) can cause A-V block, decreased cardiac output and decreased coronary flow. Bilgutay et. al experimented with various currents of different frequencies, pulse shapes and pulse widths, and noted that 10 pps and 0.2 msec pulse duration with increasing only the amplitude of the current attained very predictable changes in rate.
An International Patent Application published under the Patent Cooperation Treaty (WO 01/00273 A1; PCT/US00/17222), entitled “Devices and methods for vagus nerve stimulation”, publication date Jan. 4, 2001 ('273 application), discloses devices and methods for “electrically-induced and pharmaceutically prolonged cardiac asystole” (p. 1, I. 7-8) for controlling heart beats during cardiac surgery, and more particularly, during coronary artery by-pass surgery (CABG) when anastomatic formation is readily disrupted by a beating heart
A stated object of the '273 application is to induce asystole by applying an electrical stimulus to the vagus nerve (p. 3, I. 29-31). FIGS. 2A-B, 3A-3E, 4A-4F, and 5A-5B show electrodes for electrically inducing asystole. These Figures and their corresponding description are incorporated by reference herein for all purposes.
According to the '273 application, “[t]he chronotropic effect of vagal nerve stimulation in the absence of pharmacological potentiation includes a very brief initial pause followed by ‘vagal escape’ beats and transient bradycardia” and “[v]agus nerve stimulation alone does not produce controlled asystole” (p. 9, I. 10-14). Therefore, the '273 application relies on a combination of electrical stimulation and a pharmacological composition to produce controlled asystole. Based on the work of Bilgutay et al. (above), it is believed that electrical stimulation of the vagus nerves to the point of asystole is hemodyanmically deleterious and should be avoided.
To deliver electrical stimulation to the vagus nerve, the '273 application discloses implanting a percutaneous catheter or an electrode probe in “the internal jugular vein, trachea, esophagus, or a combination thereof” (p. 9, I.7-30). The electrodes disclosed in the '273 application generally have a basket, balloon or umbrella configuration, wherein “the optimal number of wires can vary depending upon the circumstances” and wherein “[e]ach wire is an independent electrode, electrically exposed only on its outer service at the point where it makes contact with the wall of the internal jugular vein, trachea, or esophagus” (p. 10, I. 16-20). Further, the '273 application states that a bipolar electric field can be established “between electrodes on individual devices in separate anatomical structures” such as, “a balloon, basket or umbrella . . . in the jugular vein, while another electrode is on a balloon, basket or umbrella in the trachea or in the esophagus” (p. 10, I. 33-35; p. 11, I. 1-2).
Intravenous catheters disclosed by the '273 application have “a distally disposed electrode means that can be expanded in the internal jugular vein so as to press up against the internal wall of the internal jugular vein and force contact between an electrode and the blood vessel wall” (p. 15, I. 6-9). This arrangement “allows electrical current and electrical fields to pass through the thin wall of the internal jugular vein to stimulate the vagus nerve, which lies immediately adjacent to the internal jugular vein” (p. 15, I. 9-12). According to the '273 application, for purposes disclosed therein, the “electrode means can be added to any intravascular catheter device known to one of skill in the art . . . including the Swan Ganz catheter” (p. 15, I. 12-14).
The '273 application also discloses, a cardiac monitoring device (20) connected to a patient by a connection means (21) (p. 13, I. 4-6) and a cardiac pacer device (60) for pacing the heart out of asystole and a pacer to patient connecting means (61) (p. 13, I. 35-36; p. 14, I. 1). Further, to prevent inadvertent cardiac stimulation “[t]he cardiac pacer output can be ‘off’ whenever the vagal stimulator output is ‘on’” (p. 14, I. 6-7).
Typically in the past, nerve stimulating electrodes were of the cuff-type or impalement-type. These electrodes can potentially cause irreversible nerve damage due to swelling or direct mechanical damage to the nerve, and such placement is usually performed through very invasive surgery, which produces a high risk to nerve damage.
More recently, transvenous-type electrodes have been in use, typically “floating” ring or surface electrodes along a lead body, such as that taught in U.S. Pat. No. 6,006,134 ('134 patent), entitled “Method and device for electronically controlling the beating of a heart using venous electrical stimulation of nerve fibers”, to Hill et al., issued Dec. 21, 1999. Briefly, the '134 patent discloses advancing a lead having an array of electrodes into a patient's vascular system wherein a user must selectively employ electrodes within the array to properly direct electrical pulses applied to the electrodes to desired nerve fibers. The '134 patent discloses “stimulating” (i.e., initiating a heartbeat) and “destimulating” (i.e., stopping or arresting the heartbeat). The '134 patent also discloses insertion of a selectively employed electrodes catheter “into the internal jugular vein for stimulation of the right and left vagal nerve bundle . . . into the very high internal jugular vein to stimulate the hypoglossal nerve and/or into the very low jugular vein or SVC to stimulate the phrenic nerve for respiratory control” . . . and further states “into the azygos or accessory hemiazygous veins to stimulate the sympathetic nerves for increasing heart rate” (col. 8, I. 519-23).
A known problem with these types of surface electrodes is that they can make poor contact with tissue if they are merely lying within a vessel, or adjacent a vessel. Furthermore, the orientation of the electrodes for the best contact (i.e., lowest thresholds) often has to be determined by the physician.
What is needed is an implantable stimulation lead having an electrode portion capable of making good contact with the portion of the right vagus nerve with leads to the heart for stimulating parasympathetic nerves for decreasing the atrial heart rate (and preferably, without stimulating the phrenic nerve which can evoke undesirable diaphragmatic stimulation), such as the cardiac branch site where the right vagus nerve enters into the right atrium at the level of the SVC/RA junction, or just below the azygos vein; and a method of positioning of such a lead into the azygos or hemizygos veins and providing techniques for automatically determining an appropriate stimulation level.
What is further needed is a method of automatically and gradually adapting the vagal stimulation until a desired reduction in atrial heart rate is achieved, while preserving sinus rhythm (i.e., a normal cardiac rate set by the sinus node, normally between 60 and 100 bpm) and maintaining A-V synchrony, and further capable of providing backup A-V sequential support pacing in the event that asystole occurs.
And finally, a single-pass implantable stimulation lead is needed (one that can that can stimulate the desired portion of the right vagus nerve and stimulating the right atrium, the right ventricle and/or the left ventricle) to simplify the implant procedure: a lead that can provide an orientation suitable for implantation in a patient's right azygos vein, azygos arch, and/or hemiazygos veins.